Ultimately, my objectives include learning how to approach and analyze a particular problem in a successful and original manner, gaining experience in producing quality research in the biomedical sciences, and in presenting the research in a persuasive and compelling manner. Albert Einstein College of Medicine (AECOM) has a wealth of quality research that one can participate in. This proposal will focus upon determining the importance of purine salvage enzymes using a genetic approach. Inosine metabolism via purine nucleoside phosphorylase (PNP) and hypoxanthine guanine xanthin phosphorytase (HGXPRT) is through to represent the primary pathway for purine salvage in malaria parasites. PNP and HGXPRT will be genetically disrupted in P. falciparum. Mechanisms of compensation for loss fPNP and HGXPRT will be examined using purine uptake studies and real time PCR analysis of purine salvage enzyme gene expression. Purine uptake and purine salvage enzyme gene expression wit be compared in knock-out parasites and parasites treated with specific purine salvage enzyme inhibitors. The significance of alternative purine salvage enzymes methylthioadenosine phosphorylase 0VITAP) and adenine phosphoribosyltransferase (APRT) will be examined using genetic disruption and inhibitor ablation of activity. Inhibitors designed in the Schramm and Grubmeyer laboratories will be testeed against P. falciparum cultured in human erythrocytes and in mice infected with P. yoelii, a lethal form of mouse malaria.